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Blood, 1 January 2007, Vol. 109, No. 1, pp. 259-270.
Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-03-012948.
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Submitted March 29, 2006
Accepted August 16, 2006
Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations
Kostas Stamatopoulos, Chrysoula Belessi, Carol Moreno, Myriam Boudjograh, Giuseppe Guida, Tatjana Smilevska, Lynda Belhoul, Stefania Stella, Niki Stavroyianni, Marta Crespo, Anastasia Hadzidimitriou, Laurent Sutton, Francesc Bosch, Nikolaos Laoutaris, Achilles Anagnostopoulos, Emili Montserrat, Athanasios Fassas, Guillaume Dighiero, Federico Caligaris-Cappio, Helene Merle-Beral, Paolo Ghia*, and Fred Davi
Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece
Hematology Department, Nikea General Hospital, Athens, Greece
Hospital Clinic, University of Barcelona, Barcelona, Spain
Laborary of Hematology & Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France
Institute for Cancer Research and Treatment, IRCC, Torino, Italy
Department of Clinical Hematology, Hopital Victor Dupouy, Argenteuil, France
Unite d'Immuno-Hematologie et d'Hematopathologie, Institut Pasteur, Paris, France
Universita Vita-Salute, San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy
Universita Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milano, Italy
* Corresponding author; email: ghia.paolo{at}hsr.it.
Chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201/916 CLL patients (21.9%) expressed IGHV genes which belonged to one of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised  3 sequences and were considered "confirmed". The remaining subsets comprised pairs of sequences and were considered "potential"; public-database CLL sequences were found to be members of 9/22 "potential" subsets, thereby allowing to consider them also "confirmed". The chance of belonging to a subset exceeded 35% for unmutated and/or selected IGHV genes (e.g, IGHV1-69/3-21/4-39). Comparison to non-CLL public-database sequences showed that HCDR3 restriction is "CLL-related". CLL cases with selected stereotyped IGs were also found to share unique biological and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (e.g., those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen binding site can be critical in determining the clinical features and outcome for at least some CLL patients.
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|
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|
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|
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|
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|
|
|
|
|
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|
|
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|
|
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111(3):
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|
|
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|
|
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|
|
|
|
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|
|
|
|
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